Radiosensitization by Hyperthermia Critically Depends on the Time Interval

Abstract

Background and PurposeHyperthermia is a potent sensitizer of radiotherapy that improves both tumor control and survival in women with locally advanced cervical cancer (LACC). The optimal sequence and interval between hyperthermia and radiotherapy are still under debate. Experimental designWe investigated the interval and sequence in vitro in cervical cancer cell lines and patient-derived organoids, in vivo in SiHa cervical cancer hind leg xenografts in athymic nude mice and compared the results with retrospective results from 58 women with LACC treated with thermoradiotherapy. ResultsAll three approaches confirmed that shortening the interval between hyperthermia and radiotherapy enhanced hyperthermic radiosensitization by 2 to 8 times more DNA double-strand breaks and apoptosis, 10 to 100 times lower cell survival, delayed tumor growth in mice, and increased the 5-year survival rate of women with LACC from 22% (interval ≥ 80 min) to 54% (interval <80 min). In vitro and in vivo results showed that the sequence of hyperthermia and radiotherapy did not affect the outcome. ConclusionsShortening the interval between hyperthermia and radiotherapy significantly improves treatment outcomes. The sequence of hyperthermia and radiotherapy (before or after) does not seem to matter.